Targeting Oxidative Stress to Prevent Vascular and Skeletal Muscle Dysfunction During Disuse
Joel Trinity
72 participants
Sep 1, 2019
INTERVENTIONAL
Conditions
Summary
Prolonged periods of reduced activity are associated with decreased vascular function and muscle atrophy. Physical inactivity due to acute hospitalization is also associated with impaired recovery, hospital readmission, and increased mortality. Older adults are a particularly vulnerable population as functional (vascular and skeletal muscle mitochondrial dysfunction) and structural deficits (loss in muscle mass leading to a reduction in strength) are a consequence of the aging process. The combination of inactivity and aging poses an added health threat to these individuals by accelerating the negative impact on vascular and skeletal muscle function and dysfunction. The underlying factors leading to vascular and skeletal muscle dysfunction are unknown, but have been linked to increases in oxidative stress. Additionally, there is a lack of understanding of how vascular function is impacted by inactivity in humans and how these changes are related to skeletal muscle function. It is our goal to investigate the mechanisms that contribute to disuse muscle atrophy and vascular dysfunction in order to diminish their negative impact, and preserve vascular and skeletal muscle function across all the lifespan.
Eligibility
Inclusion Criteria3
- Age between 65-85 yrs
- Ability to sign informed consent
- Montreal cognitive assessment (MOCA) exam score greater-than or equal to 26 4. Free-living, prior to admission
Exclusion Criteria27
- Cardiac abnormalities considered exclusionary by the study physician (e.g., congestive heart failure (CHF), coronary artery disease (CAD), right-to-left shunt)
- Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
- Glomerular filtration rate (GFR) less-than 30 mL/min/1.73m2 or evidence of kidney disease or failure
- Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia greater-than 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
- Risk of deep vein thrombosis (DVT) including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb greater-than 18 g/dL) or thrombocytosis (platelets greater-than 400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
- Use of anticoagulant therapy (e.g., Coumadin, heparin)
- Elevated systolic pressure greater-than 150 or a diastolic blood pressure greater-than 100 (treated or untreated)
- Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Currently on a weight-loss diet or body mass index greater-than 35 kg/m2 (a BMI of 35 kg/m2, which includes individuals that fall into to the Class I obesity category, has been selected to improve inclusion and generalizability to a greater percentage of the general population).
- Inability to abstain from smoking for duration of study
- A history of greater-than 20 pack per year smoking
- HIV or hepatitis B or C*
- Recent anabolic or corticosteroids use (within 3 months)
- Subjects with hemoglobin or hematocrit lower than accepted lab values
- Agitation/aggression disorder (by psychiatric history and exam)
- History of stroke with motor disability
- A recent history (less-than 12 months) of GI bleed
- Depression \[greater-than 5 on the 15 items Geriatric Depression Scale (GDS)\]
- Alcohol abuse (greater-than 2 drinks per day) or drug abuse (inappropriate use of prescription medications or use of any illicit/illegal drugs for recreational use)
- Exercise training (greater-than 1 session of moderate to high intensity aerobic or resistance exercise/week)
- Liver disease (aspartate aminotransferase/alanine aminotransferase 2 times above the normal limit, hyperbilirubinemia)
- Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation less-than 97% on room air)
- Currently taking a mitochondrial targeted antioxidant or similarly acting nutraceutical
- Unwilling to cease dietary supplements 4 weeks prior to initiation of bed rest
- Participated in similar bed rest study during last 12 months
- Any other condition or event considered exclusionary by the PI and faculty physician
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Interventions
Participants will receive 160 mg with breakfast on day 1 of bed rest and 40 mg with breakfast on days 2-5.
Participants will receive 100 mg on days 1-5 of bed rest.
Participants will receive Placebo on days 1-5 of bed rest.
Participants will be tested for passive leg movement on baseline day 1, bed rest day 1, and post bed rest.
Participants will undergo plantar flexion on baseline day 2, pre bed rest, and post bed rest.
Participants will undergo isometric knee extension on baseline day 2, pre bed rest, and post bed rest.
Participants will undergo 5 days bed rest after 5 day baseline assessments
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT04351113